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首页> 外文期刊>European journal of gastroenterology and hepatology >Immunomodulating and anti-apoptotic action of ursodeoxycholic acid: where are we and where should we go?
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Immunomodulating and anti-apoptotic action of ursodeoxycholic acid: where are we and where should we go?

机译：熊去氧胆酸的免疫调节和抗凋亡作用：我们在哪里，应该去哪里？

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摘要

Ursodeoxycholic acid (UDCA) is currently used in clinical practice worldwide not only for the dissolution of cholesterol gallstones, but also, mainly, to treat patients with chronic cholestatic liver diseases. However, the mechanisms of action of UDCA at the hepatocyte and cholangiolyte levels are still not completely understood. Much progress has been made from the first concept that the only mechanism of action of this bile acid was its choleretic action. One of the most fascinating mechanisms of action that was evoked for UDCA is its immunomodulating and anti-apoptotic action, which could, in part, be explained by its interaction with the glucocorticoid nuclear receptor at the hepatocyte level. Glucocorticoids, whose prototype is dexamethasone, are the major ligands of the glucocorticoid receptor. The biological effects of glucocorticoids are driven by a multiple-step reaction including binding of the steroid to the glucocorticoid receptor, DNA binding, receptor transformation, nuclear translocationand either positive or negative gene transactivation. In this issue of the journal, Weitzel and co-workers clearly demonstrated that the binding of UDCA to the glucocorticoid receptor is unspecific. Therefore, the anti-inflammatory, cytoprotective and anti-apoptotic actions of UDCA should be due not only to the mild interaction with the glucocorticoid receptor, but also to transactivation or transrepression of different cytoplasmic proteins that are involved in the survival pathway.
机译：熊去氧胆酸（UDCA）目前在全世界的临床实践中不仅用于胆固醇胆结石的溶解，而且主要用于治疗患有慢性胆汁淤积性肝病的患者。但是，UDCA在肝细胞和胆管溶液水平上的作用机理仍未完全了解。从第一个概念，即胆汁酸的唯一作用机制是其胆汁作用，已经取得了很大的进步。 UDCA引起的最引人入胜的作用机制之一是其免疫调节和抗凋亡作用，这在一定程度上可以通过其与糖皮质激素核受体在肝细胞水平上的相互作用来解释。糖皮质激素的原型是地塞米松，是糖皮质激素受体的主要配体。糖皮质激素的生物学作用由多步反应驱动，包括类固醇与糖皮质激素受体的结合，DNA结合，受体转化，核易位以及正或负基因反式激活。在该期杂志中，Weitzel及其同事清楚地证明了UDCA与糖皮质激素受体的结合是非特异性的。因此，UDCA的抗炎，细胞保护和抗凋亡作用不仅应归因于与糖皮质激素受体的轻度相互作用，还应归因于存活途径中涉及的不同细胞质蛋白的反式激活或反式抑制。

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